(E)-4-oxo-4-(3-(phenylcarbamoyl)-1H-indol-1-yl)but-2-enoic acid | 1213775-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-4-oxo-4-(3-(phenylcarbamoyl)-1H-indol-1-yl)but-2-enoic acid
• 英文别名: N-fumaroylindole-3-carboxanilide；(E)-4-oxo-4-[3-(phenylcarbamoyl)indol-1-yl]but-2-enoic acid
• CAS: 1213775-82-6
• 化学式: C₁₉H₁₄N₂O₄
• 分子量: 334.331
• InChiKey: HOWRSNQZQVCBIX-ZHACJKMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-4-oxo-4-(3-(phenylcarbamoyl)-1H-indol-1-yl)but-2-enoic acid 、 (E)-N-(5-hydroxy-3-oxapentyl)-3,4-dimethoxycinnamamide 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.67h， 以64%的产率得到(E,E)-N-[11-aza-14-(3,4-dimethoxyphenyl)-5,8-dioxa-4,12-dioxotetradeca-2,13-dienoyl]indole-3-carboxanilide
  参考文献：
  名称：

  Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?

  摘要：

  A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, L-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy) ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 mu M, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA = 89%/96%) and L-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)(2)-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 mu M, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 mu M), ACI-SPM-TRAA (7, IC50 41.5 mu M), DMCA-NH(CH2CH2O)(2)-TRAA (15, IC50 65 mu M), 13 (IC50 81.5 mu M) and ACI-dopamine (11, IC50 87 mu M). The most potent inhibitors of lipid peroxidation at 100 mu M were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 mu M) of the compounds. Conjugates 3 (IC50 2.6 mu M) and 4 (IC50 4.7 mu M) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 mu M) and ACI (IC50 14.6 mu M), whereas conjugate 15 (IC50 12.9 mu M) was less cytotoxic than either DCSP (IC50 11.3 mu M) or the tert-butyl ester of TRAA (IC50 2.9 mu M). (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.10.012
• 作为产物：
  描述：

  benzhydryl (E)-4-oxo-4-(3-(phenylcarbamoyl)-1H-indol-1-yl)but-2-enoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以85%的产率得到(E)-4-oxo-4-(3-(phenylcarbamoyl)-1H-indol-1-yl)but-2-enoic acid
  参考文献：
  名称：

  多烯间隔基中带有酰胺键的阿维A类似物的合成和抗氧化活性评估

  摘要：

  通过将苯胺与N-保护的吲哚-3-羧酸偶联，然后脱保护并与O-单保护的二羧酸偶联或吲哚-3-甲醛，3-乙酰基-1的Wittig反应合成抗银屑病药物阿维A酸酯的酯类似物。 -甲苯磺酰基吡咯和4-氨基-9-芴酮与Ph 3 P CHCO 2 tBu，然后在必要时进行N-脱保护，最后与肉桂酰氟偶合。通过TFA介导的羧基脱保护得到相应的游离酸。虽然这些类似物和阿维A表现出非常低的还原能力，类似物5，6，8和12强烈抑制LOX带IC 50值范围从35–65μM。阿维A和它的类似物5 - 7，10，11和15抑制脂质过氧化的比更强烈水溶性维生素E而阿维A和模拟4是在体内更有效的抗发炎剂上诱导卡拉胶比吲哚美辛的大鼠爪水肿。

  DOI：

  10.1016/j.ejmech.2009.10.012

文献信息

• Does conjugation of antioxidants improve their antioxidative/anti-inflammatory potential?
  作者：Dimitra Hadjipavlou-Litina、George E. Magoulas、Stavros E. Bariamis、Denis Drainas、Konstantinos Avgoustakis、Dionissios Papaioannou

  DOI：10.1016/j.bmc.2010.10.012

  日期：2010.12

  A series of symmetric and asymmetric spermine (SPM) conjugates with all-trans-retinoic acid (ATRA), acitretin (ACI), (E)-3-(trioxsalen-4'-yl)acrylic acid (TRAA) and L-DOPA, amides of ACI, L-DOPA and TRAA with 1-aminobutane, benzylamine, dopamine and 1,12-diaminobutane as well as hybrid conjugates of O,O'-dimethylcaffeic acid (DMCA) with TRAA or N-fumaroyl-indole-3-carboxanilide (FICA) and 2-(2-aminoethoxy) ethanol were synthesized and their antioxidant properties were studied. The reducing activity (RA)% of the compounds were evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging assay and found to be in the range 0-92(20 min)%/96(60 min)% at 100 mu M, the most powerful being the conjugates L-DOPA-SPM-L-DOPA (8, RA = 89%/96%) and L-DOPA-dopamine (13, RA = 92%/92%). Conjugate DMCA-NH(CH2CH2O)(2)-FICA (14) was the most powerful LOX inhibitor with IC50 33.5 mu M, followed by the conjugates ACI-NHCH2Ph (10, IC50 40.5 mu M), ACI-SPM-TRAA (7, IC50 41.5 mu M), DMCA-NH(CH2CH2O)(2)-TRAA (15, IC50 65 mu M), 13 (IC50 81.5 mu M) and ACI-dopamine (11, IC50 87 mu M). The most potent inhibitors of lipid peroxidation at 100 mu M were the conjugates 15 (98%) and ACI-SPM-ACI (4, 97%) whereas all other compounds showed activities comparable or lower than trolox. The most interesting compounds, namely ATRA-SPM-ATRA (3), 4, 10, 11 and 15, as well as unconjugated compounds such as ATRA and dopamine, were studied for their anti-inflammatory activity in vivo on rat paw oedema induced by Carrageenan and found to exhibit, for doses of 0.01 mmol/mL of conjugates per Kg of rat body weight, weaker anti-inflammatory activities (3.6-40%) than indomethacin (47%) with conjugate 3 being the most potent (40%) in this series of compounds. The cytocompatibility of selected compounds was evaluated by the viability of RAMEC cells in the presence of different concentrations (0.5-50 mu M) of the compounds. Conjugates 3 (IC50 2.6 mu M) and 4 (IC50 4.7 mu M) were more cytotoxic than the corresponding unconjugated retinoids ATRA (IC50 18.3 mu M) and ACI (IC50 14.6 mu M), whereas conjugate 15 (IC50 12.9 mu M) was less cytotoxic than either DCSP (IC50 11.3 mu M) or the tert-butyl ester of TRAA (IC50 2.9 mu M). (C) 2010 Elsevier Ltd. All rights reserved.
• Syntheses and evaluation of the antioxidant activity of acitretin analogs with amide bond(s) in the polyene spacer
  作者：Dimitra Hadjipavlou-Litina、George E. Magoulas、Marios Krokidis、Dionissios Papaioannou

  DOI：10.1016/j.ejmech.2009.10.012

  日期：2010.1

  Ester analogs of the antipsoriatic drug acitretin were synthesized by coupling either anilines with N-protected indole-3-carboxylic acid, followed by deprotection and coupling with O-monoprotected dicarboxylic acids or Wittig reaction of indole-3-carboxaldehyde, 3-acetyl-1-tosylpyrrole and 4-amino-9-fluorenone with Ph3PCHCO2tBu, followed by N-deprotection, where necessary, and finally coupling with

  通过将苯胺与N-保护的吲哚-3-羧酸偶联，然后脱保护并与O-单保护的二羧酸偶联或吲哚-3-甲醛，3-乙酰基-1的Wittig反应合成抗银屑病药物阿维A酸酯的酯类似物。 -甲苯磺酰基吡咯和4-氨基-9-芴酮与Ph 3 P CHCO 2 tBu，然后在必要时进行N-脱保护，最后与肉桂酰氟偶合。通过TFA介导的羧基脱保护得到相应的游离酸。虽然这些类似物和阿维A表现出非常低的还原能力，类似物5，6，8和12强烈抑制LOX带IC 50值范围从35–65μM。阿维A和它的类似物5 - 7，10，11和15抑制脂质过氧化的比更强烈水溶性维生素E而阿维A和模拟4是在体内更有效的抗发炎剂上诱导卡拉胶比吲哚美辛的大鼠爪水肿。